Showing papers in "Neurology in 2020"

Miller Fisher syndrome and polyneuritis cranialis in COVID-19.

Abstract: Objective: To report two patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) who acutely presented with Miller Fisher syndrome and polyneuritis cranialis, respectively. Methods: Patient data were obtained from medical records from the University Hospital “Principe de Asturias”, Alcala de Henares, Madrid, Spain and from the University Hospital “12 de Octubre”, Madrid, Spain. Results: The first patient was a 50-year-old man who presented with anosmia, ageusia, right internuclear ophthalmoparesis, right fascicular oculomotor palsy, ataxia, areflexia, albuminocytologic dissociation and positive testing for GD1b-IgG antibodies. Five days before, he had developed a cough, malaise, headache, low back pain, and a fever. The second patient was a 39-year-old man who presented with ageusia, bilateral abducens palsy, areflexia and albuminocytologic dissociation. Three days before, he had developed diarrhea, a low-grade fever, and a poor general condition. The oropharyngeal swab test for coronavirus disease 2019 (COVID-19) by qualitative real-time reverse-transcriptase–polymerase-chain-reaction assay was positive in both patients and negative in the cerebrospinal fluid. The first patient was treated with intravenous immunoglobulin and the second, with acetaminophen. Two weeks later, both patients made a complete neurological recovery, except for residual anosmia and ageusia in the first case. Conclusions: Our two cases highlight the rare occurrence of Miller Fisher syndrome and polyneuritis cranialis during the COVID-2 pandemic. Neurological manifestations may occur because of an aberrant immune response to COVID-19. The full clinical spectrum of neurological symptoms in patients with COVID-19 remains to be characterized.

Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry.

Abstract: Objective: The coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019. Neurological symptoms have been reported as part of the clinical spectrum of the disease. We aim to determine whether neurological manifestations are common in hospitalized COVID-19 patients and to describe their main characteristics. Methods: We systematically review all patients diagnosed with COVID-19 admitted to hospital in a Spanish population during March 2020. Demographic characteristics, systemic and neurological clinical manifestations, and complementary tests were analyzed. Results: Of 841 patients hospitalized with COVID-19 (mean age 66.4 years, 56.2% men) 57.4% developed some form of neurological symptom. Nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were present mostly in the early stages of infection. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early (60% as the first clinical manifestation) and were more frequent in less severe cases. Disorders of consciousness occurred commonly (19.6%), mostly in older patients and in severe and advanced COVID-19 stages. Myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), movement disorders (0.7%), encephalitis (n=1), Guillain-Barre syndrome (n=1), and optic neuritis (n=1) were also reported, but less frequent. Neurological complications were the main cause of death in 4.1% of all deceased study subjects. Conclusions: Neurological manifestations are common in hospitalized COVID-19 patients. In our series, more than half of patients presented some form of neurological symptom. Clinicians need to maintain close neurological surveillance for prompt recognition of these complications. The investigation of the mechanisms and emerging consequences of SARS-CoV-2 neurological involvement require further studies.

Research criteria for the diagnosis of prodromal dementia with Lewy bodies

Abstract: The prodromal phase of dementia with Lewy bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation.

Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.

Abstract: OBJECTIVE: To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury. METHODS: We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort. RESULTS: The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury. CONCLUSION: We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.

Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study

Abstract: Objective The phase IIIb A Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Participants With Relapsing Forms of Multiple Sclerosis (VELOCE) study (NCT02545868) assessed responses to selected vaccines in ocrelizumab (OCR)-treated patients with relapsing multiple sclerosis. Methods Patients were randomized 2:1 into the OCR group (n = 68; OCR 600 mg) or control group (n = 34; interferon beta or no disease-modifying therapy). All received tetanus toxoid (TT)-containing vaccine, Pneumovax (23-valent pneumococcal polysaccharide vaccine [23-PPV]), and keyhole limpet hemocyanin (KLH). The OCR group was subdivided into OCR1 (n = 33) and OCR2 (n = 35) at randomization. The OCR1 group received Prevnar (13-valent conjugate pneumococcal vaccine) 4 weeks after 23-PPV; the OCR2 and control groups received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (OCR group) or on day 1 (control group). Results Positive response rate to TT vaccine at 8 weeks was 23.9% in the OCR vs 54.5% in the control group. Positive response rate to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in the OCR and 100% in the control group. Prevnar did not enhance response to pneumococcal serotypes in common with Pneumovax. Humoral response to KLH was decreased in the OCR vs control group. Seroprotection rates at 4 weeks against 5 influenza strains ranged from 55.6% to 80.0% in the OCR2 group and 75.0% to 97.0% in the control group. Conclusion Peripherally B-cell–depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen KLH, suggesting that use of standard nonlive vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR because a potentially protective humoral response, even if attenuated, can be expected. Classification of evidence This study provides Class II evidence confirming that the humoral response to nonlive vaccines in patients with relapsing multiple sclerosis after OCR treatment is attenuated compared with untreated or interferon beta–treated patients, but they can still be expected to be protective. Clinicaltrials.gov identifier NCT02545868.

COVID-19 presenting with ophthalmoparesis from cranial nerve palsy.

Abstract: Neurologic complications of COVID-19 are not well described. We report 2 patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

Abstract: OBJECTIVE To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER NCT00572195. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

COVID-19 and neuromuscular disorders.

Abstract: The coronavirus 2019 (COVID-19) pandemic has potential to disproportionately and severely affect patients with neuromuscular disorders. In a short period of time, it has already caused reorganization of neuromuscular clinical care delivery and education, which will likely have lasting effects on the field. This article reviews (1) potential neuromuscular complications of COVID-19, (2) assessment and mitigation of COVID-19-related risk for patients with preexisting neuromuscular disease, (3) guidance for management of immunosuppressive and immunomodulatory therapies, (4) practical guidance regarding neuromuscular care delivery, telemedicine, and education, and (5) effect on neuromuscular research. We outline key unanswered clinical questions and highlight the need for team-based and interspecialty collaboration. Primary goals of clinical research during this time are to develop evidence-based best practices and to minimize morbidity and mortality related to COVID-19 for patients with neuromuscular disorders.

Telemedicine in neurology: Telemedicine Work Group of the American Academy of Neurology update

Abstract: Purpose While there is strong evidence supporting the importance of telemedicine in stroke, its role in other areas of neurology is not as clear. The goal of this review is to provide an overview of evidence-based data on the role of teleneurology in the care of patients with neurologic disorders other than stroke. Recent findings Studies across multiple specialties report noninferiority of evaluations by telemedicine compared with traditional, in-person evaluations in terms of patient and caregiver satisfaction. Evidence reports benefits in expediting care, increasing access, reducing cost, and improving diagnostic accuracy and health outcomes. However, many studies are limited, and gaps in knowledge remain. Summary Telemedicine use is expanding across the vast array of neurologic disorders. More studies are needed to validate and support its use.

Early postmortem brain MRI findings in COVID-19 non-survivors.

Abstract: Objectives: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuro-invasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). This study investigates the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework. Methods: In this prospective, monocentric, case series study, consecutive patients who fulfilled the following inclusion criteria benefited from an early postmortem structural brain MRI: death Results: Among the 62 patients who died from COVID-19 from 31/03/2020 to 24/04/2020 at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent). Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality was observed. Conclusions: Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. Brainstem MRI findings do not support a brain-related contribution to respiratory distress in COVID-19.

Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2

Abstract: Objective To evaluate the efficacy and safety of eptinezumab, a humanized anti–calcitonin gene-related peptide monoclonal antibody, in the preventive treatment of chronic migraine (CM). Methods The Prevention of Migraine via Intravenous ALD403 Safety and Efficacy–2 (PROMISE-2) study was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults with CM were randomly assigned to receive IV eptinezumab 100 mg, eptinezumab 300 mg, or placebo administered on day 0 and week 12. The primary endpoint was change from baseline in mean monthly migraine days (MMDs) over weeks 1 to 12. Results Among treated participants (n = 1,072), baseline mean number of MMDs was ≈16.1 across groups. Treatment with eptinezumab 100 and 300 mg was associated with significant reductions in MMDs across weeks 1 to 12 compared with placebo (placebo −5.6, 100 mg −7.7, p 2% of eptinezumab-treated patients at an incidence of >2% over placebo; it occurred in the 300 mg eptinezumab arm (eptinezumab 9.4%, placebo 6.0%). Conclusion In patients with CM, eptinezumab 100 and 300 mg was associated with a significant reduction in MMDs from the day after IV administration through week 12, was well tolerated, and demonstrated an acceptable safety profile. Classification of evidence This study provides Class I evidence that for patients with CM, a single dose of eptinezumab reduces MMDs over 12 weeks of treatment. ClinicalTrials.gov identifier NCT02974153.

Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy.

Abstract: Objective To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19). Methods In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period. Results One hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0–83.8 years vs 70.1 years, IQR 52.9–78.6 years, p = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7–1.1 vs 0.5, IQR 0.4–0.6, p = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, p Conclusions Patients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.

Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy.

Abstract: Objective To report safety, pharmacokinetics, exon 53 skipping, and dystrophin expression in golodirsen-treated patients with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping. Methods Part 1 was a randomized, double-blind, placebo-controlled, 12-week dose titration of once-weekly golodirsen; part 2 is an ongoing, open-label evaluation. Safety and pharmacokinetics were primary and secondary objectives of part 1. Primary biological outcome measures of part 2 were blinded exon skipping and dystrophin protein production on muscle biopsies (baseline, week 48) evaluated, respectively, using reverse transcription PCR and Western blot and immunohistochemistry. Results Twelve patients were randomized to receive golodirsen (n = 8) or placebo (n = 4) in part 1. All from part 1 plus 13 additional patients received 30 mg/kg golodirsen in part 2. Safety findings were consistent with those previously observed in pediatric patients with DMD. Most of the study drug was excreted within 4 hours following administration. A significant increase in exon 53 skipping was associated with ∼16-fold increase over baseline in dystrophin protein expression at week 48, with a mean percent normal dystrophin protein standard of 1.019% (range, 0.09%–4.30%). Sarcolemmal localization of dystrophin was demonstrated by significantly increased dystrophin-positive fibers (week 48, p Conclusion Golodirsen was well-tolerated; muscle biopsies from golodirsen-treated patients showed increased exon 53 skipping, dystrophin production, and correct dystrophin sarcolemmal localization. Clinicaltrials.gov identifier NCT02310906. Classification of evidence This study provides Class I evidence that golodirsen is safe and Class IV evidence that it induces exon skipping and novel dystrophin as confirmed by 3 different assays.

Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium.

Abstract: OBJECTIVE: To determine changes in the incidence of dementia between 1988 and 2015. METHODS: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex. RESULTS: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%]). CONCLUSION: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations.

Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid.

Abstract: Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis The patient received IV immunoglobulins and plasma exchange Her neurologic status improved, and she was extubated 4 weeks after symptom onset This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms

Neurologic complications of coronavirus infections.

Abstract: In 1896, Sir William Osler1 said, “Humanity has but three great enemies: fever, famine, and war; of these by far the greatest, by far the most terrible, is fever.” This rings true even today.

Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study.

Abstract: Objective To describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations. Methods In this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI. Results The cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20–92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome (p = 0.006) and more frequently had corticospinal tract signs (p = 0.02). Patients with encephalitis were younger (p = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement (p = 0.009). Conclusions Patients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF. ClinicalTrials.gov identifier NCT04368390.

Treating multiple sclerosis and neuromyelitis optica spectrum disorder during the COVID-19 pandemic.

Abstract: The emergence of novel coronavirus 2019 (COVID-19)1 and the subsequent pandemic present a unique challenge to neurologists managing patients with multiple sclerosis (MS) and related neuroinflammatory disorders, such as neuromyelitis spectrum disorder (NMOSD).

Biological subtypes of Alzheimer disease: A systematic review and meta-analysis

Abstract: Objective To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data. Methods EMBASE, PubMed, and Web of Science databases were consulted until July 2019. Results Neuropathology and neuroimaging studies have consistently identified 3 subtypes of AD based on the distribution of tau-related pathology and regional brain atrophy: typical, limbic-predominant, and hippocampal-sparing AD. A fourth subtype, minimal atrophy AD, has been identified in several neuroimaging studies. Typical AD displays tau-related pathology and atrophy both in hippocampus and association cortex and has a pooled frequency of 55%. Limbic-predominant, hippocampal-sparing, and minimal atrophy AD had a pooled frequency of 21%, 17%, and 15%, respectively. Between-subtype differences were found in age at onset, age at assessment, sex distribution, years of education, global cognitive status, disease duration, APOE e4 genotype, and CSF biomarker levels. Conclusion We identified 2 core dimensions of heterogeneity: typicality and severity. We propose that these 2 dimensions determine individuals9 belonging to one of the AD subtypes based on the combination of protective factors, risk factors, and concomitant non-AD brain pathologies. This model is envisioned to aid with framing hypotheses, study design, interpretation of results, and understanding mechanisms in future subtype studies. Our model can be used along the A/T/N classification scheme for AD biomarkers. Unraveling the heterogeneity within AD is critical for implementing precision medicine approaches and for ultimately developing successful disease-modifying drugs for AD.

Clinical risk factors in SUDEP: A nationwide population-based case-control study.

Abstract: Objective We conducted a nationwide case-control study in Sweden to test the hypothesis that specific clinical characteristics are associated with increased risk of sudden unexpected death in epilepsy (SUDEP). Methods The study included 255 SUDEP cases (definite and probable) and 1,148 matched controls. Clinical information was obtained from medical records and the National Patient Register. The association between SUDEP and potential risk factors was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) and interaction assessed by attributable proportion due to interaction (AP). Results Experiencing generalized tonic-clonic seizures (GTCS) during the preceding year was associated with a 27-fold increased risk (OR 26.81, 95% CI 14.86–48.38), whereas no excess risk was seen in those with exclusively non-GTCS seizures (OR 1.15, 95% CI 0.54–48.38). The presence of nocturnal GTCS during the last year of observation was associated with a 15-fold risk (OR 15.31, 95% CI 9.57–24.47). Living alone was associated with a 5-fold increased risk of SUDEP (OR 5.01, 95% CI 2.93–8.57) and interaction analysis showed that the combination of not sharing a bedroom and having GTCS conferred an OR of 67.10 (95% CI 29.66–151.88), with AP estimated at 0.69 (CI 0.53–0.85). Among comorbid diseases, a previous diagnosis of substance abuse or alcohol dependence was associated with excess risk of SUDEP. Conclusions Individuals with GTCS who sleep alone have a dramatically increased SUDEP risk. Our results indicate that 69% of SUDEP cases in patients who have GTCS and live alone could be prevented if the patients were not unattended at night or were free from GTCS.

Global prevalence and burden of HIV-associated neurocognitive disorder: A meta-analysis.

Abstract: Objective To characterize the prevalence and burden of HIV-associated neurocognitive disorder (HAND) and assess associated factors in the global population with HIV. Methods We searched PubMed and Embase for cross-sectional or cohort studies reporting the prevalence of HAND or its subtypes in HIV-infected adult populations from January 1, 1996, to May 15, 2020, without language restrictions. Two reviewers independently undertook the study selection, data extraction, and quality assessment. We estimated pooled prevalence of HAND by a random effects model and evaluated its overall burden worldwide. Results Of 5,588 records identified, we included 123 studies involving 35,513 participants from 32 countries. The overall prevalence of HAND was 42.6% (95% confidence interval [CI] 39.7–45.5) and did not differ with respect to diagnostic criteria used. The prevalence of asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia were 23.5% (20.3–26.8), 13.3% (10.6–16.3), and 5.0% (3.5–6.8) according to the Frascati criteria, respectively. The prevalence of HAND was significantly associated with the level of CD4 nadir, with a prevalence of HAND higher in low CD4 nadir groups (mean/median CD4 nadir Conclusions Our findings suggest that people living with HIV have a high burden of HAND in the antiretroviral therapy (ART) era, especially in sub-Saharan Africa and Latin America. Earlier initiation of ART and sustained adherence to maintain a high-level CD4 cell count and prevent severe immunosuppression is likely to reduce the prevalence and severity of HAND.

Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection.

Abstract: Objective To report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) who acutely developed a hypokinetic-rigid syndrome. Methods Patient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum. Results We report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS–CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment. Conclusion This case study provides clinical and functional neuroimaging evidence to support that SARS–CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.

Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder.

Abstract: Objective Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments. Methods We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy. Results Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% Conclusion This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.

COVID-19 is catalyzing the adoption of teleneurology.

Abstract: The coronavirus disease of 2019, or COVID-19, changed the world within a matter of weeks. The primary action to constrain the spread of the virus is social isolation. Given this public health principle, and the shortage of personal protective equipment during the global pandemic, all health care stakeholders need to reconsider the indications for face-to-face health care encounters in providing patient care. Which encounters are imperative and which ones can be switched to non–face-to-face care? What changes in laws, regulations, payment policies, and workflow are needed to enable this transition?1–3

Long-Haul COVID.

Abstract: Modern medicine has faced its biggest challenge from the smallest of organisms. It is becoming increasingly apparent that many patients who recovered from the acute phase of the SARS-CoV-2 infection have persistent symptoms. This includes clouding of mentation, sleep disturbances, exercise intolerance and autonomic symptoms (table 1). Some also complain of persistent low grade fever and lymphadenopathy. Although there are no peer reviewed papers at the moment on these patients, many news articles have been written about this phenomenon1–4 and there are Facebook groups with several thousand patients describing these symptoms. They call the illness, “Long-Haul COVID” or “Long-tail COVID.” Many of these patients are health care workers who had massive exposure to the virus early in the pandemic and describe having symptoms for “100+ days.”5

Bilateral transient olfactory bulb edema during COVID-19-related anosmia.

Abstract: An asymptomatic 27-year-old man was diagnosed with coronavirus disease 2019 (COVID-19) by occupational medicine after contagion (reverse transcription polymerase chain reaction [ RT - PCR ]). Four days after the diagnosis, he experienced complete anosmia and dysgeusia.1 On day 7, 1.5T MRI showed signs of bilateral olfactory bulb edema on 3D constructive interference in steady state T2-weighted imaging, demonstrated by severe enlargement2 (left: 73 mm3, right: 64 mm3) and an abnormally high signal intensity (figure). Olfactory clefts showed mild edema. The olfactory pathways, including the cortical projections (fluid-attenuated inversion recovery and diffusion-weighted imaging not shown), were normal. Sensory recovery and negative RT-PCR (positive on days 1, 2, and 10) appeared on day 14. MRI on day 24 confirmed the normalization of olfactory bulb signal and volumes (left: 22 mm3, right: 17 mm3).

Keeping people with epilepsy safe during the COVID-19 pandemic.

Abstract: OBJECTIVES: To provide information on the effect of the coronavirus disease of 2019 (COVID-19) pandemic on people with epilepsy and provide consensus recommendations on how to provide the best possible care for people with epilepsy while avoiding visits to urgent care facilities and hospitalizations during the novel coronavirus pandemic. METHODS: The authors developed consensus statements in 2 sections. The first was "How should we/clinicians modify our clinical care pathway for people with epilepsy during the COVID-19 pandemic?" The second was "What general advice should we give to people with epilepsy during this crisis? The authors individually scored statements on a scale of -10 (strongly disagree) to +10 (strongly agree). Five of 11 recommendations for physicians and 3/5 recommendations for individuals/families were rated by all the authors as 7 or above (strongly agree) on the first round of rating. Subsequently, a teleconference was held where statements for which there was a lack of strong consensus were revised. RESULTS: After revision, all consensus recommendations received a score of 7 or above. The recommendations focus on administration of as much care as possible at home to keep people with epilepsy out of health care facilities, where they are likely to encounter COVID-19 (including strategies for rescue therapy), as well as minimization of risk of seizure exacerbation through adherence, and through ensuring a regular supply of medication. We also provide helpful links to additional helpful information for people with epilepsy and health providers. CONCLUSION: These recommendations may help health care professionals provide optimal care to people with epilepsy during the coronavirus pandemic.

Scoping review of prevalence of neurologic comorbidities in patients hospitalized for COVID-19.

Abstract: Objective The emergence of coronavirus disease 2019 (COVID-19) presents a challenge for neurologists caring for patients with preexisting neurologic conditions hospitalized for COVID-19 or for evaluation of patients who have neurologic complications during COVID-19 infection. We conducted a scoping review of the available literature on COVID-19 to assess the potential effect on neurologists in terms of prevalent comorbidities and incidence of new neurologic events in patients hospitalized with COVID-19. Methods We searched MEDLINE/PubMed, CINAHL (EBSCO), and Scopus databases for adult patients with preexisting neurologic disease who were diagnosed and hospitalized for COVID-19 or reported incidence of secondary neurologic events following diagnosis of COVID-19. Pooled descriptive statistics of clinical data and comorbidities were examined. Results Among screened articles, 322 of 4,014 (8.0%) of hospitalized patients diagnosed and treated for COVID-19 had a preexisting neurologic illness. Four retrospective studies demonstrated an increased risk of secondary neurologic complications in hospitalized patients with COVID-19 (incidence of 6%, 20%, and 36.4%, respectively). Inconsistent reporting and limited statistical analysis among these studies did not allow for assessment of comparative outcomes. Conclusion Emerging literature suggests a daunting clinical relationship between COVID-19 and neurologic illness. Neurologists need to be prepared to reorganize their consultative practices to serve the neurologic needs of patients during this pandemic.

New onset neurologic events in people with COVID-19 in 3 regions in China.

Abstract: OBJECTIVE: To investigate new-onset neurologic impairments associated with coronavirus disease 2019 (COVID-19) METHODS: A retrospective multicenter cohort study was conducted between January 18 and March 20, 2020, including people with confirmed COVID-19 from 56 hospitals officially designated in 3 Chinese regions; data were extracted from medical records New-onset neurologic events as assessed by neurology consultants based on manifestations, clinical examination, and investigations were noted, in which critical events included disorders of consciousness, stroke, CNS infection, seizures, and status epilepticus RESULTS: We enrolled 917 people with average age 487 years and 55% were male The frequency of new-onset critical neurologic events was 35% (32/917) overall and 94% (30/319) among those with severe or critical COVID-19 These were impaired consciousness (n = 25) or stroke (n = 10) The risk of critical neurologic events was highly associated with age above 60 years and previous history of neurologic conditions Noncritical events were seen in fewer than 1% (7/917), including muscle cramp, unexplained headache, occipital neuralgia, tic, and tremor Brain CT in 28 people led to new findings in 9 Findings from lumbar puncture in 3 with suspected CNS infection, unexplained headache, or severe occipital neuralgia were unremarkable CONCLUSIONS: People with COVID-19 aged over 60 and with neurologic comorbidities were at higher risk of developing critical neurologic impairment, mainly impaired consciousness and cerebrovascular accidents Brain CT should be considered when new-onset brain injury is suspected, especially in people under sedation or showing an unexplained decline in consciousness Evidence of direct acute insult of severe acute respiratory syndrome coronavirus 2 to the CNS is lacking

Time course and diagnostic utility of NfL, tau, GFAp, and UCH-L1 in subacute and chronic TBI

Abstract: Objective: To determine if neurofilament light (NfL), glial fibrillary acidic protein (GFAp), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI. Methods: Patients with TBI (n=162) and controls (n=68) were prospectively enrolled between 2009–2018. Of the 162 patients, 102 underwent repeated serum, functional outcome, brain MRI volumetry, and DTI assessments at 30, 90, and 180 days, and 1, 2, 3, 4, and 5 years after TBI. Results: At enrolment, patients with TBI had increased serum NfL compared to controls (p Conclusions: Serum NfL shows greater diagnostic and prognostic utility than GFAp, tau, and UCH-L1 for subacute and chronic TBI. Classification of Evidence: This study provides Class III evidence that serum NfL distinguishes patients with mild TBI from healthy controls.